In six male alcoholic volunteers, oral administration of calcium carbimide (0.7 mg/kg) before ingestion of ethanol (0.5 g/kg) produced an interaction consisting of increased blood acetaldehyde level, tachycardia and increased pulse pressure, which was due mainly to decreased diastolic blood pressure. For these experimental conditions, calcium carbimide had a duration of action of at least 24 h to produce an interaction with ethanol. The order of intensity of the interaction with regard to the calcium carbimide pretreatment time interval was 4 greater than 8 approximately 12 greater than 24 h. Using the criterion of heart rate above 100 as indicative of the calcium carbimide-ethanol interaction, the onset was 0.13, 0.25, 0.25 and 0.38 h for the 4-, 8-, 12- and 24-h pretreatment experiments and the duration of the interaction was 1.6, 1.0, 1.0 and 0.12 h, respectively. There were positive linear correlations between acetaldehyde level and heart rate and between acetaldehyde level and pulse pressure. There was appreciable interindividual variability in the heart rate and blood pressure responses. Increased blood acetaldehyde level seemed to be required for the physiological changes to occur. Calcium carbimide pretreatment at the 4-h interval produced increased blood ethanol level for the last hour of the interaction and reduced the rate of ethanol metabolism.
A simple and reliable method was developed for rating the dose-related behavioural effects of methamphetamine in male Swiss Albino mice for acute or chronic drug treatment. This procedure was based on a frequency count of certain behaviours made at 15-min intervals over a 90-min period following drug administration. The Fisher Randomization procedure was adapted to analyze behavioural data for the chronic studies. Clear-cut, dose-related behavioural responses occurred following acute (+)-methamphetamine administration and ranged from decreased quiescence (0.64 mg/kg) through increased locomotor activity (2.5 mg/kg), a mixture of stereotyped behaviour and increased locomotor activity (5.0 and 7.5 mg/kg), to primarily stereotyped gnawing, licking or sniffing (10 mg/kg). In studies involving chronic administration of (+)-methamphetamine at 0.64, 2.5 and 10 mg/kg conducted over six and seven weeks, behavioural responses were more exaggerated than in acute studies. All behaviours returned to normal levels in the recovery week except for locomotor activity at the 10 mg/kg dosage. In some animals, chronic treatment with 10 mg/kg (+)-methamphetamine led to protracted self-tearing that replaced the gnawing, licking, sniffing stereotype.
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